KR920702223A - 1-cycloalkylpiperidine as an antipsychotic - Google Patents

Abstract

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Description

1-cycloalkylpiperidine as an antipsychotic

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Claims (73)

A compound of formula (I) or a pharmaceutically acceptable salt thereof. Wherein m, n and p are 0 to 3, provided that both m and n are not 0, X is O, S, SO, SO ₂ , NR ⁶ , CR ⁷ R ⁸ , CO or CHOH, R ¹ , R ³ and R ⁷ are independently H, alkyl of 1 to 5 carbon atoms, halogen, NR ¹⁰ R ¹¹ , OH, CO ₂ H carboalkoxy of 2 to 6 carbon atoms, CN, Ar ¹ , 1 to 5 carbon atoms Alkoxy or alkylthio having 1 to 5 carbon atoms, R ² R ⁴ and R ⁸ are independently H, alkyl having 1 to 5 carbon atoms, carboalkoxy having 2 to 6 carbon atoms, CN, alkoxy having 1 to 5 carbon atoms or Ar ¹ Provided that when X is O, S, SO, SO ₂ , or NR ⁶ , R ¹ , R ² , R ³ and R ⁴ are alkoxy having 1 to 5 carbon atoms, alkylthio having 1 to 5 carbon atoms, NR ¹⁰ R Is not ¹¹ or OH, R ⁵ is H, alkyl, halogen, OH or alkenyl, R ⁶ is H, alkyl of 1 to 5 carbon atoms or Ar ¹ , Ar and Ar ¹ are independently alkyl of 1 to 3 carbon atoms , Having 1 to 3 carbon atoms and 1 to 7 halogen atoms Haloalkyl having, SH, S (O) _t alkyl having 1 to 3 carbon atoms, wherein t is 1,2 or 3, dialkylamino having 2 to 6 carbon atoms, halogen, OH, alkyl having 1 to 3 carbon atoms Amino, NH ₂ , CN, NO ₂ , SO ₃ H, tetrazole, CO ₂ , carboalkoxy having 2 to 6 carbon atoms, CONH ₂ , SO ₂ NH ₂ , COR ⁹ , CONR ¹² R ¹³ , SO ₂ NR ¹² R ¹³ , Ar ^2, OAr ^2, or SAr by ^two optionally substituted naphthyl, pyridyl, pyrimidyl, indolyl, quinolinyl, iso quinolinyl, and carbonyl or phenyl, Ar ² is an alkyl, having 1 to 3 carbon atoms Is haloalkyl having 1 to 3 and having 1 to 7 halogen atoms, alkoxy having 1 to 3 carbon atoms, halogen or naphthyl or phenyl optionally substituted with alkylthio having 1 to 3 carbon atoms, R ⁹ , R ¹⁰ , R ^11, R ¹² and R ¹³ are independently, H, alkyl or phenyl group having 1 to 5, R ¹⁰ and R ¹¹ is R ¹² and R ¹³ together form an alkylene chain having 3 to 6 carbon atoms, or Together form an alkylene chain having 3 to 6 carbon atoms and, a and b is a double bond or a single bond, independently, with the proviso that not both of both the double bond. The compound of claim 1, wherein X is CO, O or CHOH. The compound of claim 1, wherein m is zero. The compound of claim 1, wherein n and p are each 1. The compound of claim 1, wherein R ³ and R ⁵ are H. ⁷ . The compound of claim 1, wherein Ar is phenyl optionally substituted by halogen, OCH ₃ , NH ₂ , NO ₂ or another phenyl group. The compound of claim 1 wherein X is CO, O or CHOH, m is 0, n and p are each 1, R ³ and R ⁵ are H, and Ar is halogen, OCH ₃ , NH ₂ , NO ₂ or A compound which is phenyl optionally substituted by another phenyl group. 8. A compound according to claim 7, wherein X is CO. 8. A compound according to claim 7, wherein Ar is 4-fluorophenyl. 8. The compound of claim 7, wherein X is CO, n and p are each 1, R ³ , R ⁴ and R ⁵ are H and Ar is 4-fluorophenyl. 8. A compound according to claim 7, wherein X is O. 8. The compound of claim 7, wherein X is O, m is 0, n and p are each 1, R ³ , R ⁴ and R ⁵ are H and Ar is 4-fluorophenyl. The compound of claim 1, which is 1- (cyclopropylmethyl) -4- (2 '-(4 "-fluorophenyl) -2'-oxoethyl) piperidine. A compound according to claim 1, which is a salt which is 1- (cyclopropylmethyl) -4- (2 '-(4 "-fluorophenyl) -2'-oxoethyl) piperidine hydrobromide. The compound of claim 1, which is 1- (cyclopropylmethyl) -4- (2 '-(4 "-chlorophenyl) -2'-oxoethyl) piperidine. The compound according to claim 1, which is 1- (cyclopropylmethyl) -4- (2 '-(4 "-chlorophenyl) -2'-oxoethyl) piperidine, hydrobromide salt. The compound of claim 1, which is 1- (cyclopropylmethyl) -4- (4′-fluorophenoxymethyl) piperidine. A compound according to claim 1, which is 1- (cyclopropylmethyl) -4- (4'-fluorophenoxymethyl) piperidine, hydrochloride salt. The compound of claim 1, which is 1- (cyclopropylmethyl) -4- (4′-chlorophenoxymethyl) piperidine. A compound according to claim 1, which is 1- (cyclopropylmethyl) -4- (4'-chlorophenoxymethyl) piperidine, hydrochloride salt. The compound of claim 1, which is 1- (cyclopropylmethyl) -4- (4′-nitrophenoxymethyl) piperidine. The compound of claim 1, which is 1- (cyclopropylmethyl) -4- (2 '-(4'-biphenyl) -2'-oxoethyl) piperidine. A compound according to claim 1, which is 1- (cyclopropylmethyl) -4- (2 '-(4'-biphenyl) -2'-oxoethyl) piperidine, hydrobromide salt. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 1 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 2 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 3 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 4 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 5 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 6 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 7 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 8 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 9 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 10 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 11 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 12 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 13 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 14 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 15 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 16 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 17 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 18 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 19 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 20 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 21 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 22 and a pharmaceutically acceptable carrier. A pharmaceutical composition comprising a therapeutically effective amount of a psychosis compound of claim 23 and a pharmaceutically acceptable carrier. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 1. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 2. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 3. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 4. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 5. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 6. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 7. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 8. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 9. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 10. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 11. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 12. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 13. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 14. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 15. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 16. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 17. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 18. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 19. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 20. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 21. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of psychosis or a therapeutically effective amount of the compound of claim 22. A method of treating a mammal's physiological or drug-induced psychosis or movement disorder, characterized by administering to the mammal a therapeutically effective amount of a psychosis or a therapeutically effective amount of the compound of claim 23. Compound of formula (IV). In the above formula, m and n are 0 to 3, except that all are not 0, p is 1 to 3, X is O, S or NR ⁶ , and Ar and Ar ¹ are each independently 1 to 3 carbon atoms. Alkyl, alkoxy having 1 to 3 carbon atoms, haloalkyl having 1 to 3 carbon atoms and having 1 to 7 halogen atoms, S (O) _t alkyl having 1 to 3 carbon atoms, where t is 1,2 or 3, Dialkylamino of 2 to 6 carbon atoms, halogen, OH, alkylamino of 1 to 3 carbon atoms, CN, NO ₂ , dialkylamino of 2 to 6 carbon atoms, carboalkoxy of 2 to 6 carbon atoms, COR ⁹ , CONR ¹² R ¹³ , Naphthyl, pyridyl, pyrimidyl, quinolinyl, isoquinolinyl or phenyl optionally substituted by SO ₂ NR ¹² R ¹³ Ar ² , or SAr ² , Ar ² is alkyl having 1 to 3 carbons, carbon atoms Is haloalkyl having 1 to 3 and having 1 to 7 halogen atoms, alkoxy having 1 to 3 carbon atoms, halogen or alkylthio having 1 to 3 carbon atoms Optionally substituted naphthyl or phenyl, R ¹ to R ⁴ and R ⁶ are independently H, alkyl of 1 to 5 carbon atoms, or Ar ¹ , R ⁵ is H, alkyl, halogen, OH or alkenyl, R ⁹ , R ¹² and R ¹³ are independently H, alkyl of 1 to 5 carbon atoms or phenyl, or R ¹² and R ¹³ together form an alkylene chain of 3 to 6 carbon atoms. (a) m is 1, CR ¹ R ² is CO and X is O, S, NR ⁶ or CH ₂ a compound of formula (II) in combination with a compound of formula (III) in the presence of a base and an inert solvent; Reacting to prepare a compound of formula (IV). Ar (CR ¹ R ² ) _m XH (II) Wherein m, n, p, Ar, X, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined in claim 70, Y is a halide, arylsulfonyloxy, alkylsulfonyloxy, Haloalkyl sulfonyloxy or acyloxy. A compound of formula (IV) prepared by the method of claim 71 is reduced by using a reducing agent in an inert solvent, wherein X is O, S, CHOH or NR ⁶ , wherein R ⁶ is And a compound of formula (I). (a) The compound of formula (VII) is treated with an alkylating agent of formula (VII) to form a compound of formula (VII), and (b) the compound of formula (VII) produced is reduced to form a general formula Process for preparing the compound of (I). Wherein m, n, p, Ar, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined in claim 1, X is CO or CHCH, Z is halogen, arylsulfonyloxy or Haloalkylsulfonyloxy. ※ Note: The disclosure is based on the initial application.